Potential Role of Circulating MiR-21 in the Diagnosis and Prognosis of Digestive System Cancer

Yin, Chengqiang; Zhou, Xiaoying; Dang, Yini; Yan, Jin; Zhang, Guoxin

doi:10.1097/md.0000000000002123

Cited by 26 publications

(16 citation statements)

References 51 publications

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“…Furthermore, it has been reported that miR-21-5p is upregulated in patients aged >40 years who underwent gastrectomy for potentially curable GC (stage III) and experienced a recurrence ( 43 ). In addition, a meta-analysis study indicated that elevated miR-21 expression levels are correlated with tumor differentiation, lymph node metastasis and TNM stage in digestive tract cancer ( 44 ), which is consistent with the results of the present study.…”

Section: Discussionsupporting

confidence: 92%

miR‑21‑5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3

Zhou

Xiang

et al. 2018

Int J Mol Med

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Drug resistance and disease recurrence are major obstacles to the effective treatment of cancer, including gastric cancer (GC). However, the mechanisms of drug resistance remain to be fully elucidated. The present study investigated the roles of microRNA (miR)-21-5p in the doxorubicin (DOX) resistance of GC cells and the underlying mechanisms. miR-21-5p expression levels were identified to be inversely correlated with two well-known tumor suppressor genes, phosphatase and tensin homologue and tissue inhibitor of matrix metalloproteinases 3, and were upregulated in GC cell lines in proportion to their degree of resistance. Suppressing miR-21-5p expression partially sensitized SGC7901/DOX cells to DOX, suggesting that knockdown of miR-21-5p expression may be used as a therapeutic strategy to improve GC cell resistance. Importantly, increased miR-21-5p expression levels at diagnosis were correlated with clinicopathological characteristics including advanced stage and poor prognosis, further implying that a relapse of GC may be a consequence of miR-21-5p upregulation, thus providing evidence for the potential utility of miR-21-5p antagonism to sensitize GC cells to DOX chemotherapy.

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Section: Discussionsupporting

confidence: 92%

miR‑21‑5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3

Zhou

Xiang

et al. 2018

Int J Mol Med

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“…The observation that miR-21 is highly expressed in the plasma of patients with metastatic neuroendocrine tumors is consistent with its known function and with findings in other malignancies [ 2 ]. Expression of miR-21 has been shown to be associated with proliferation, apoptosis and migration [ 31 ] and involved in invasion, intravasation and metastasis [ 32 , 33 ]. miR-21 is upregulated in glioblastoma [ 34 ], breast cancer [ 35 , 36 ], lung cancer [ 37 ], gastric cancer [ 38 ], colorectal cancer [ 39 ], hepatocellular carcinoma [ 40 ], pancreatic cancer [ 41 ] as well as other tumor types [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

Profiling of metastatic small intestine neuroendocrine tumors reveals characteristic miRNAs detectable in plasma

et al. 2017

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BackgroundCurrent diagnostic and prognostic blood-based biomarkers for neuroendocrine tumors are limited. MiRNAs have tumor-specific expression patterns, are relatively stable, and can be measured in patient blood specimens. We performed a multi-stage study to identify and validate characteristic circulating miRNAs in patients with metastatic small intestine neuroendocrine tumors, and to assess associations between miRNA levels and survival.MethodsUsing a 742-miRNA panel, we identified candidate miRNAs similarly expressed in 19 small intestine neuroendocrine tumors and matched plasma samples. We refined our panel in an independent cohort of plasma samples from 40 patients with metastatic small intestine NET and 40 controls, and then validated this panel in a second, large cohort of 120 patients with metastatic small intestine NET and 120 independent controls.ResultsmiRNA profiling of 19 matched small intestine neuroendocrine tumors and matched plasma samples revealed 31 candidate miRNAs similarly expressed in both tissue and plasma. We evaluated expression of these 31 candidate miRNAs in 40 independent cases and 40 normal controls, and identified 4 miRNAs (miR-21-5p, miR-22-3p, miR-29b-3p, and miR-150-5p) that were differently expressed in cases and controls (p<0.05). We validated these 4 miRNAs in a separate, larger panel of 120 cases and 120 controls. We confirmed that high circulating levels of miR-22-3p (p<0.0001), high levels of miR 21-5p, and low levels of miR-150-5p (p=0.027) were associated with the presence of metastatic small intestine NET. While levels of 29b-3p were lower in cases than in controls in both the initial cohort and the validation cohort, the difference in the validation cohort did not reach statistical significance. We further found that high levels of circulating miR-21-5p, high levels of circulating miR-22-3p and low levels of circulating miR-150-5p were each independently associated with shorter overall survival. A combined analysis using all three markers was highly prognostic for survival (HR 0.47, 95% CI 0.27-0.82).ConclusionsOur study suggests that elevated circulating levels of miR-21-5p and miR-22-3p and low levels of miR-150-5p are characteristic in patients with metastatic small intestine neuroendocrine tumors, and further suggests that levels of these miRNAs are associated with overall survival. These observations provide the basis for further validation studies, as well as studies to assess the biological function of these miRNAs in small intestine neuroendocrine tumors.

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“…miR-21, which promotes cell proliferation and invasion and is upregulated in many cancers, is one of the most widely investigated miRNAs. 67 , 68 , 69 , 70 In HER2-positive BC, miR-21 was found to be inversely correlated with the expression of PTEN and PDCD4; by triggering an interleukin-6 (IL-6)/STAT3/nuclear factor κB (NF-κB)-mediated signaling loop and activating the PI3K pathway, it is also related to decreased trastuzumab sensitivity. 71 Blocking the action of miR-21 with antisense oligonucleotides (ASOs) re-sensitized resistant cells to the therapeutic effects of trastuzumab.…”

Section: Main Textmentioning

confidence: 99%

Potential Regulatory Roles of MicroRNAs and Long Noncoding RNAs in Anticancer Therapies

Xie

et al. 2018

Molecular Therapy - Nucleic Acids

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MicroRNAs and long noncoding RNAs have long been investigated due to their roles as diagnostic and prognostic biomarkers of cancers and regulators of tumorigenesis, and the potential regulatory roles of these molecules in anticancer therapies are attracting increasing interest as more in-depth studies are performed. The major clinical therapies for cancer include chemotherapy, immunotherapy, and targeted molecular therapy. MicroRNAs and long noncoding RNAs function through various mechanisms in these approaches, and the mechanisms involve direct targeting of immune checkpoints, cooperation with exosomes in the tumor microenvironment, and alteration of drug resistance through regulation of different signaling pathways. Herein we review the regulatory functions and significance of microRNAs and long noncoding RNAs in three anticancer therapies, especially in targeted molecular therapy, and their mechanisms.

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Potential Role of Circulating MiR-21 in the Diagnosis and Prognosis of Digestive System Cancer

Abstract: Supplemental Digital Content is available in the text

Cited by 26 publications

References 51 publications

miR‑21‑5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3

miR‑21‑5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3

Profiling of metastatic small intestine neuroendocrine tumors reveals characteristic miRNAs detectable in plasma

Potential Regulatory Roles of MicroRNAs and Long Noncoding RNAs in Anticancer Therapies

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